Depressive symptoms and poor health perceptions are predictors of higher hospitalization and mortality rates (heart failure [HF]). However, the association between depressive symptoms and health perceptions as they affect event-free survival outcomes in patients with HF has not been studied. The purpose of this secondary analysis was to determine whether depressive symptoms mediate the relationship between health perceptions and event-free survival in patients with HF. A total of 458 HF patients (61.6 ± 12 years, 55% New York Heart Association Class III/IV) responded to one-item health perception question and completed the Patient Health Questionnaire–9. Event-free survival data were collected for up to 4 years. Multiple regression and Cox proportional hazards regression analysis showed that depressive symptoms mediated the relationship between health perceptions and event-free survival. Decreasing depressive symptoms is essential to improve event-free survival in patients with HF.